Ellis-van Creveld syndrome, also known as chondroectodermal dysplasia, is a rare inherited disorder that affects the development of bones and cartilage. It is a form of skeletal dysplasia, characterized by abnormalities in the skeleton’s growth and structure. This leads to a range of physical characteristics, most notably a form of short-limbed dwarfism.
The condition impacts multiple systems, extending beyond the skeleton to affect the development of nails, teeth, and the heart. While motor skills and intelligence are normal, the associated health issues, particularly those involving the heart and lungs, can present significant challenges from birth.
Genetic Causes and Inheritance Patterns
Mutations in either the EVC or the EVC2 gene are responsible for the condition. These two genes are located very close to each other on the short arm of chromosome 4. Their proteins play a role in a cell-to-cell communication system called the Sonic Hedgehog signaling pathway, which is active during embryonic development and helps shape bones, teeth, and other body parts.
The inheritance pattern for this syndrome is autosomal recessive, which means an affected child must inherit two copies of the mutated gene—one from each parent. The parents, known as carriers, each carry one copy of the mutated gene and do not show signs of the disorder.
This syndrome is well-known for its high frequency in the Old Order Amish population of Lancaster County, Pennsylvania. This is a result of the “founder effect,” a genetic phenomenon that occurs when a new population is established by a small number of individuals. The original carriers of the EVC mutation in this community have been traced back to a single couple who immigrated to the area in 1744, leading to a much higher prevalence of the syndrome within this genetically isolated group.
Key Physical Characteristics
The physical traits of Ellis-van Creveld syndrome are distinct and often recognizable at birth. One of the most prominent features is disproportionate short-limbed dwarfism. Specifically, the middle and lower segments of the limbs—the forearms and lower legs—are significantly shorter than the upper arms and thighs, a pattern referred to as mesomelic shortening, which results in an adult height ranging from 3.5 to 5 feet.
Nearly all individuals with the syndrome are born with post-axial polydactyly, which is the presence of extra fingers on the side of the hand next to the pinky finger. Extra toes may also be present in about one-third of cases.
The syndrome also involves ectodermal dysplasia, the abnormal development of structures derived from the ectoderm, an outer layer of the early embryo. This manifests as malformed fingernails and toenails, which are often small, underdeveloped, or spoon-shaped. Dental abnormalities are also common and can include teeth that are present at birth, small or peg-shaped teeth, and a higher susceptibility to cavities.
Approximately 60% of individuals with Ellis-van Creveld syndrome are born with a congenital heart defect. The presence of a cardiac anomaly from birth is a defining feature of the syndrome.
Associated Health Complications
The high incidence of congenital heart defects is a primary concern, with the most common issue being a large atrial septal defect (ASD) or a condition where the atria are not separated, known as a common atrium. These structural problems affect blood flow between the heart and lungs and often require surgical intervention.
Respiratory issues are also prevalent, especially in infancy. The chest is often narrow and the ribs are short, which can restrict lung growth and function. This can lead to breathing difficulties and an increased risk of respiratory infections. In some newborns, the restrictive lung disease may be severe enough to require mechanical ventilation.
Skeletal and orthopedic issues can arise over time and affect mobility. Many individuals develop genu valgum, a condition commonly known as knock-knees, where the knees angle inward. This condition can be progressive and may require surgical procedures, such as osteotomies, to realign the bones. Other orthopedic concerns can include malformations of the wrist bones and dislocation of the radial head at the elbow.
The associated dental abnormalities create lifelong challenges. Issues like missing or malformed teeth, along with abnormal attachments between the gums and lip, can interfere with feeding and speech development. These problems require specialized dental and orthodontic care to manage oral health and ensure proper function.
Diagnosis and Medical Management
Diagnosis can often be made before birth. Prenatal ultrasounds may reveal indicators such as shortened limbs, a narrow chest, and polydactyly. If these signs are present, or if there is a known family history, the diagnosis can be confirmed through genetic testing like amniocentesis, which analyzes fetal DNA for mutations in the EVC or EVC2 genes. After birth, diagnosis is based on observable physical features and confirmed with X-rays and genetic testing.
There is no cure, so medical management focuses on treating the specific symptoms and complications. This requires a coordinated, multidisciplinary team of specialists. Cardiologists manage and treat congenital heart defects, while pulmonologists address respiratory issues stemming from the narrow chest.
Orthopedic surgeons are involved in monitoring and correcting skeletal problems, such as performing surgery to remove extra digits or to address severe knock-knees. Specialized dentists and orthodontists are needed to manage the complex dental issues, from removing natal teeth that interfere with feeding to providing long-term care for malformed or missing teeth. With proactive and comprehensive care, many individuals who survive the risks of infancy can lead full lives.